Linked Life Data

12975495

Source:http://linkedlifedata.com/resource/pubmed/id/12975495

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-10-22
pubmed:abstractText
It is therapeutically desirable to effectively deliver ceramide, an antimitogenic and proapoptotic lipid second messenger, to transformed cell types. However, the targeted delivery of cell-permeable ceramide analogs, including C6-ceramide, to cells may be impeded by the hydrophobicity of these bioactive lipids, resulting in reduced efficacy. The objective of this study is to develop and optimize liposomal vehicles to augment ceramide delivery to a breast adenocarcinoma cell line. We designed conventional, cationic, and pegylated drug release vesicles to efficaciously deliver ceramide to MDA-MB-231 breast adenocarcinoma cells. In vitro pharmacokinetic analysis demonstrated that liposomal ceramide delivery resulted in significantly greater accumulation of ceramide in MDA-MB-231 cells. Ceramide-formulated liposomes significantly inhibited MDA-MB-231 cell proliferation as compared with nonliposomal administration of ceramide. Ceramide-induced apoptosis correlated with the pharmacokinetic profile and the diminished proliferation in this highly aggressive, metastatic cell line. Liposomal ceramide formulations inhibited phosphorylated Akt levels and stimulated caspase-3/7 activity more effectively than nonliposomal ceramide, events consistent with apoptosis. Together, these results indicate that bioactive ceramide analogs can be incorporated into conventional, cationic, or pegylated liposomal vehicles for improved drug delivery and release.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
307
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
468-75
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Liposomal delivery enhances short-chain ceramide-induced apoptosis of breast cancer cells.
pubmed:affiliation
Department of Pharmacology, Penn State College of Medicine, P.O. Box 850, Hershey, PA 17033, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't